Cytokine Biomarkers Can Diagnose Multiple Sclerosis, Study Suggests

New research has identified cytokine biomarkers that could potentially be used to diagnose multiple sclerosis (MS) with a high degree of accuracy.

The findings, published in the journal Mediators of Inflammation, could also help distinguish progressive and relapsing remitting forms of the disease, though with a lower degree of certainty.

Corresponding author Svetlana F. Khailboullina, MD, PhD, of the University of Nevada, Reno, and colleagues explained that autoreactive leukocytes cause the brain damage that leads to debilitation in patients with MS, and leukocytes are regulated by cytokines, which can be found in the serum and and cerebrospinal fluid (CSF) of patients.

Thus, the investigators hypothesized that an analysis of cytokine levels in the serum and CSF of patients with MS might be a meaningful diagnostic marker. To find out, they analyzed serum and CSF samples from 101 patients with MS (28 males and 73 females, with a median age of 35.6 years), and compared those samples to CSF samples from 25 controls who did not have MS (9 males and 16 females with a median age of 38.5 years).

Those patients had a variety of diagnoses, including tension headaches, residual encephalopathy, and unspecified demyelinating disease of the central nervous system. In addition, serum samples from 101 subjects without MS were collected as an additional control group. All of the samples were analyzed by multiplex immunoassay in order to determine levels of 45 cytokines.

The investigators found 22 altered cytokines in the CSF of the MS group, and 20 altered cytokines in the serum samples. Those data were fed into a machine learning model in order to predict and classify MS.

The analysis showed that, by selecting any random 5 of the biomarkers, the model was able to predict MS with accuracy of 92% or greater. However, the predictive ability was even higher when the 5 cytokines chosen for analysis included CCL27, IFN-γ, and IL-4. In such cases, accuracy of MS diagnosis was 99%, the authors reported.

Khailboullina and colleagues said the correlation suggests those cytokines have an important role in the pathogenesis of MS. They said that is particularly notable in the case of CCL27, which has previously been identified as a possible factor in MS pathogenesis.

“Although these data provide limited evidence of the link between CCL27 and MS pathology, our observation of the high level of this cytokine in MS serum and CSF suggests its role in the pathogenesis of the disease,” they said.

The models were also able to diagnose type of MS. By analyzing 20 serum cytokines and 22 CSF cytokines, the models identified primary progressive and secondary progressive MS with an accuracy of 70%-78% and relapsing remitting MS with an accuracy of 60%-69%, respectively.

Finally, the investigators said they were interested to see that some cytokines were differently affected in serum and CSF.

“Two of these cytokines, IL-1β and IL-18, are the product of activated inflammasome, regulating inflammatory response,” they said. “These findings support the key role of inflammation in brain pathology and, also, supports the use of inflammasome inhibitors as therapeutic for MS.”

The authors said their model’s accuracy makes it a meaningful diagnostic tool as well as a meaningful data point in understanding how the disease begins and runs its course.

Reference

Martynova E, Goyal M, Johri S, et al. Serum and Cerebrospinal Fluid Cytokine Biomarkers for Diagnosis of Multiple Sclerosis. Mediators Inflamm. Published online October 22, 2020. doi:10.1155/2020/2727042